Evaluation of the flavonoid oroxylin A as an inhibitor of P-glycoprotein-mediated cellular efflux

Woon Jung Go, Jong Hoon Ryu, Fu Qiang, Hyo Kyung Han

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Oroxylin A (1), a flavonoid from the roots of Scutellaria baicalensis, increased the cellular accumulation of calcein AM in a concentration-dependent manner in NCI/ADR-RES cells overexpressing P-glycoprotein over the concentration range 0-40 μM. In addition, 1 significantly (p < 0.05) increased the cellular accumulation of paclitaxel in NCI/ADR-RES cells while it did not alter the cellular accumulation of paclitaxel in cells lacking P-glycoprotein expression. Accordingly, the concentrations that yielded 50% cytotoxicity of vinblastine and paclitaxel were reduced by approximately 5-fold in the presence of 1. This indicated that cancer cells became more susceptible to the cytotoxicity of vinblastine and paclitaxel in the presence of 1. The concomitant use of 1 (30 mg·kg-1) significantly (p < 0.05) enhanced the oral exposure of paclitaxel (15 mg·kg-1) in rats. The Cmax and AUC values of paclitaxel increased by 2.1-2.6-fold in the presence of 1 with no significant change in Tmax. In conclusion, 1 was effective in inhibiting P-glycoprotein-mediated drug efflux both in vitro and in vivo, suggesting that it may be useful to improve the cellular availability of P-glycoprotein substrates such as anticancer drugs.

Original languageEnglish
Pages (from-to)1616-1619
Number of pages4
JournalJournal of Natural Products
Volume72
Issue number9
DOIs
StatePublished - 25 Sep 2009

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